Vascular endothelial growth factor (VEGF) induces endothelial cell proliferation, migration, and a host of cellular responses that are necessary for angiogenesis. The effects of VEGF on gene expression in endothelial cells have been well characterized, and many of the chemical pathways have been elucidated. Similarly, VEGF is known to impact cytoskeletal structure and cellular motility. Here, we show that VEGF influences cytoskeletal-nuclear interaction by imaging human umbilical vein endothelial cells treated with VEGF. We visualize increased actin fibers present at the nucleus in VEGF treated cells. We also quantify increased fluctuations at the nuclear envelope with VEGF-treatment. This manifests itself as both a gross nuclear fluctuations, quantifiable as changes in nuclear area, and fine fluctuations, which can be visualized over several hours. Further, we observe an increase in intranuclear velocity of chromatin-bound probes. Our findings suggest enhanced mechanical coupling between the cytoskeleton and nucleus under VEGF treatment, which may have implications in the mechanobiology of altered gene expression during angiogenesis.
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We acknowledge G. Yang (Carnegie Mellon University, Department of Biomedical Engineering) for aid in image analysis development, J. Szymanski and A. Feinberg (Carnegie Mellon University, Department of Biomedical Engineering) for help with confocal imaging, and S. Kumar (UC Berkeley, Department of Bioengineering) for reagents. This work is supported by the NSF (NSF-CBET-0954421, CMMI-1300476 to KND) and CMU fellowship support to STS (ARCS, Bertucci, and Meade).
Conflict of interest
Stephen T. Spagnol, James S. Weltz, Yongqiang Xue, and Kris Noel Dahl declare that they have no conflicts of interest.
No human studies were carried out by the authors for this article. No animal studies were carried out by the authors for this article.
Stephen T. Spagnol, James S. Weltz, and Yongqiang Xue contributed equally to this work.
Associate Editor Michael R. King oversaw the review of this article.
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Spagnol, S.T., Weltz, J.S., Xue, Y. et al. Mechanical Coupling of the Endothelial Cytoskeleton and Nucleus with VEGF Stimulation. Cel. Mol. Bioeng. 7, 225–230 (2014). https://doi.org/10.1007/s12195-014-0327-x